Biomedical Pressure Sensing System

ABSTRACT

A biomedical pressure sensing system comprising a contact lens; a flexible resonator embedded in the contact lens; and a measuring means for transmitting and receiving signals and measuring differences between the transmitted signal and the received signal. The purpose of this invention is to provide a sensor which is electrically passive, wireless and low cost to measure intraocular pressure.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of application Ser. No.15/674,588 filed on Aug. 11, 2017.

TECHNICAL FIELD

This invention relates to sensors, more specifically, relates to asplit-ring resonator-based strain sensor on flexible substrates forglaucoma detection.

BACKGROUND

Wireless strain measurement attracts attention of many researchers andfinds application in numerous fields when it comes to materialcharacterization. In civil engineering, the sensors of the sort are usedto ensure maintenance in infrastructure, by measuring the strain on thestructure and take precaution in case of any abnormal strain (T.Nagayama, M. Ruiz-Sandoval, B. F. Spencer Jr., K. A. Mechitov, G. Agha,“Wireless Strain Sensor Development for Civil Infrastructure”, Trans. ofthe Society of Instrument and Control Engineers, Vol. E-3, No. 1,104/109 (2004)). In biomedical engineering, these sensors are utilizedby observation of the healing process of a fractured bone (R. Melik, N.K. Pekgoz, E. Unal, C. Puttlitz, and H. V. Demir, “Bio Implantablepassive on-chip RF-MEMS strain sensing resonators for orthopaedicapplications,” J. Micromech. Microeng. 18(11), 115017 (2008)). Moreover,in aerospace industry, wireless strain measurement comes into prominencein crack or abnormal strain detection on metal surfaces (Rajni, A. Kaur,A Marwaha, “Crack Detection on Metal Surfaces with an Array ofComplementary Split Ring Resonators”, International Journal of ComputerApplications (0975-8887) Volume 119—No. 10, June 2015). SRR-basedsensors have been demonstrated for wireless strain measurementpreviously. The resonant frequency of the device strongly depends on thegeometry of the ring and any deviation in geometry due to externalstrain applied to the device results in change in resonant frequency ofthe resonator. This enables strain measurement through the observationof the shift in resonant frequency.

Glaucoma is an eye disease, which may damage the optic nerves and leadsto vision loss. Even though it might be caused by different factors, inmost of the patients, it is caused by the increase of intraocularpressure and might eventually cause irreversible blindness. Today, thereare several different methods to detect the symptoms of glaucoma, suchas measuring central corneal thickness, measuring peripheral vision,examining the optic nerve and measuring the eyeball pressure (“FiveCommon Glaucoma Tests”, glaucoma.org, Glaucoma Research Foundation, Apr.22, 2013). It was demonstrated that the radius of curvature of thesclera is well correlated with the intraocular pressure, while theradius of the curvature of the cornea is insensitive to the changes inintraocular pressure (B. K. Pierscionek, M. Asejczyk-Widlicka, R. A.Schachar, “The effect of changing incraocular pressure on the cornealand scleral curvatures in the fresh porcine eye”, Br J Ophthalmol 2007;91:801-803. doi: 10.1136/bjo.2006.110221). Noninvasive monitoring of theintraocular pressure has been demonstrated using piezoresistive (M.Leonardi, P. Leuenberger, D. Bertrand, A. Bertsch, P. Renaud, “FirstSteps toward Noninvasive Intraocular Pressure Monitoring with a SensingContact Lens”, Invest. Ophthalmol. Vis. Sci., 45(9), 3113 (2004)) andcapacitive (D. Piso, P Veiga-Crespo, E. Vecino, “Modem MonitoringIntraocular Pressure Sensing Devices Based on Application SpecificIntegrated Circuits”, Journal of Biomaterials and Nanobiotechnology,2012, 3, 301-309) sensors embedded on soft contact lenses. It ispossible to monitor the progress of the disease in noninvasive andcontinuous manner using this approach. However, these sensors areelectrically active and require application of electrical signals in thecontact lens during operation. In addition, the system on the contactlens also includes a transmission circuitry to send the signals to anexternal unit.

Conventional methods of glaucoma detection using contact lenses employelectrically active sensors and readout electronics embedded with thelenses (M. Leonardi, P. Leuenberger, D. Bertrand, A. Bertsch, P. Renaud,“First Steps toward Noninvasive Intraocular Pressure Monitoring with aSensing Contact Lens”, Invest. Ophthalmol. Vis. Sci., 45(9), 3113(2004)). The sensors should be powered up electrically to operate andthe processed data should be transferred using wireless RF links. Thisposes a significant limitation for the systems to be integrated oncontact lenses that are in continuous contact with eye, First, it is notdesirable to have electrically active circuits in contact with eye.Secondly, the power requirement for these systems can be demanding. Inaddition, both packaging and the implementation of the sensor withintegrated readout electronics are expensive for a disposable sensor.

SUMMARY

The purpose of this invention is to provide a sensor which iselectrically passive, wireless and low cost to measure intraocularpressure. The sensor on the lens does not require any electrical signalto operate and are interrogated by external antennas that can be locatedaway from the contact lens. We use silver conductive paint to define therings on flexible substrates. This is very advantageous to defineflexible strain sensors that are required for applications as glaucomadetection.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1A shows the front view of a sensor of one embodiment of theinvention.

FIG. 1B shows the front view of a sensor of another embodiment of theinvention.

FIG. 1C shows the simulated distribution of surface current density forthe device at resonance.

FIG. 1D shows the simulated s21 spectrum of the device.

FIG. 2A shows the three-dimensional drawing of the experimental setupfor the SRR sensor realized on latex rubber.

FIG. 2B shows s21 the spectra of the device as the curvature (lip)increases.

FIG. 2C shows the variation of the resonant frequency as a function ofradius of curvature.

DETAILED DESCRIPTION OF THE INVENTION

Hereinafter this invention will be further described in conjunction withthe accompanying figures and embodiments.

The sensor that is a metallic ring can be placed on a contact lens usingstandard methods of metal deposition (sputtering, evaporation, etc.)using a shadow mask. Alternatively inkjet printing for metals can beused. The sensors can be encapsulated inside the polymeric structure ofthe contact lens using lamination.

The ring is placed on a contact lens that conforms the surface of theeye. A change in intraocular pressure results in a change in radius ofcurvature of the ring. For example, an increase in pressure increasesthe radius of curvature. Likewise, a decrease in pressure decreases theradius of curvature. Thus, the effective capacitance and inductance ofthe ring changes result in a change in the resonant frequency. Theequations are valid for the calculation of the nominal resonantfrequency of the ring and give an overall understanding of the resonantfrequency.

Split-ring resonators (SRRs) behave like RLC circuits but in most casesthe material is chosen so that the resistance value is negligible. Hencethe structure might be reduced to LC resonator and the value of resonantfrequency might be calculated by Equation 1.

$\begin{matrix}{f_{0} = \frac{1}{2\pi \sqrt{LC}}} & (1)\end{matrix}$

The inductance of the ring is expressed in equation 2 as a function ofgeometrical parameters.

$\begin{matrix}{L = {\mu_{0}{R_{m}\left( {{\log \frac{8R_{m}}{h + w}} - \frac{1}{2}} \right)}}} & (2)\end{matrix}$

where μ₀ is the free-space permeability, R_(m) is the effective radiusof the ring, w and h are the width and the height of the ring,respectively.

The capacitance of the ring has two components, the gap capacitance andsurface capacitance. The gap capacitance is calculated as follows:

$\begin{matrix}{C_{gap} = {{ɛ_{0}\frac{hw}{g}} + C_{0}}} & (3)\end{matrix}$

where ε₀ is the free-space permittivity. C₀ is the capacitance caused bythe fringing fields and can be calculated as C₀=ε₀(h+w+g). Equation 3assumes that the ring is in free-space. If the ring is placed on orembedded into a dielectric substrate, then the effective permittivity ofthe medium should be considered in this equation.

The resonant frequency of the ring is used as the sensing parameter.Changes in structural parameters affect the capacitance of the sensormore than its inductance. An increase in gap (g in Equation 3) resultsin an increase in capacitance. That results in a decrease in resonantfrequency (equation 1). On the other hand, increases in width (w) andheight (h) of the sensor result in an increase in capacitance, so adecrease in resonant frequency.

The geometry of the SRR structure is determined so that it can be placedaround the boundary between cornea and sclera where the change inintraocular pressure can be measured effectively to diagnose glaucoma.In addition, the sensor is optimized for S-band (2-4 GHz) of theelectromagnetic band.

FIG. 1A shows a photograph of sensor 10 placed on a flexible substratemade of cellulose acetate. Gap region 103 may be extended to increasethe gap capacitance and to keep the resonant frequency of the device inS-band. We applied silver conductive paint (SCP, Electrolube, UnitedKingdom) to define the ring using a hard mask on the substrate. Thethickness of ring 101 is 500 μm and the other relevant geometricalparameters are shown in FIG. 1A. For example, the width of ring 101 is1.5 mm. The width of gap region 103 is 1 mm. The gap extension L is 3.5mm. We prepared another type of sensor on a spherically deformedsubstrate made of latex rubber with a thickness of 50 μm. Using a hardmask on a spherical substrate is not possible, so we painted the ring onthe second substrate.

In a preferred embodiment, the painted or the printed ring is embeddedin a contact lens. The sensor layer is laminated inside the polymericstructure of the contact lens. As described above, an increase inintraocular pressure results in an increase in radius of curvature ofthe contact lens that conforms the eyeball. Thus, painted (or theprinted) ring on the surface of the contact lens expands. This resultsin changes in the geometry of the deformed ring. The resonant frequencyof the ring is determined by the geometrical parameters of the ring, sothe resonant frequency changes as a result of a change in intraocularpressure.

FIG. 1B shows another design of sensor 20 with similar geometricalparameters as that shown in FIG. 1A. As shown in FIG. 1B, sensor 20 mayinclude ring 201 and gap region 203. The principles of the sensor 20 aresimilar with those of sensor 10 as shown in FIG. 1A. Thus, they are notrepeated hereinafter.

We simulated the device using commercially available electromagneticsimulation software (CST Microwave Studio, Darmstadt, Germany) to obtainits scattering parameters. We performed the simulations in time domain.

FIG. 1C shows the surface current density along the conductor path atthe resonant frequency observed at 2.54 GHz. The magnetic field isperpendicular to the surface of the device for the simulation thatsupports the circulating current at resonance.

Observation of circular pattern in current density indicates that theresonance is due to magnetic field coupled to the resonator. The colorsin FIG. 1C indicate the strength of current density. The legend showsthe observed values of current density. The change in radius ofcurvature of the resonator due to intraocular pressure alters thecurrent density.

FIG. 1D shows the s21 spectrum of the device with these settings. Asshown in FIG. 1D, s21 spectrum of the measurement exhibit a sharp dip atthe resonant frequency of the sensor. Any change in resonant frequencyof the ring due to the changes in intraocular pressure results in ashift in the location of the dip. This change can be measured using theantenna pair by obtaining the scattering parameters.

We used the second setup to characterize the SRR sensor realized on thesubstrate of latex rubber.

FIG. 2A shows the experimental setup where substrate 305 is stretched ontop of a cylindrical injection syringe with a diameter of 9 mm. Thesyringe is used to pump air in and out of the device. First, the air ispumped through air port 309 so that the radius of the curvature ofsubstrate 305 becomes 13 mm. Then, the SRR structure is painted on thesurface and its s21 spectrum is obtained using the vector networkanalyzer. Following measurements by evacuating 0.2 ml air at each stepis performed, obtaining the s21 spectrum of the device. The inflateddevice shrinks with decreasing air volume so does the radius of thecurvature.

As shown in FIG. 2A, the resonant frequency of ring 307 is measuredusing an antenna pair (301, 303) that transmit and receiveelectromagnetic radiation at the frequency of the resonator. The antennapair can be placed within the vicinity of the contact lens (not shown).In a preferred embodiment, the antenna pair is placed on eyeglasses (notshown). The contact lens (not shown) is located between the transmitterantenna and the receiver antenna. The scattering parameters are measuredbetween the antennas 301 and 303.

There are two antennas 301 and 303 in the pair. Transmitting antenna 301is serve as a transmitter, and receiving antenna 303 is the receiver.

The transmitted signal passes through ring 307 of the the passivesensor. The sensor characteristics alter the signal passing throughitself.

The antennas are the ports for the measurement circuit (not shown). Afundamental measurement technique is implemented to measure scatteringparameters (s-parameters) between the ports. S-parameters are commonlyused to measure electrical characteristics between the ports at radiofrequencies (RF). A vector network analyzer is used to measure theelectrical characteristics. A power signal is applied to thetransmitting antenna 301 (port-1) and the frequency of the applied powersignal is swept using a synthesized sweeper. The applied signal isconverted to a propagating electromagnetic wave at the transmittingantenna 301. The receiving antenna 303 (port-2) captures the propagatedelectromagnetic wave and the wave is converted an electrical signal atport-2 (receiving antenna 303). S21 spectrum is obtained by comparingthe amplitude of the phase of the received signal at port-2 (receivingantenna 303) with respect to the input voltage applied to port-I(transmitting antenna 301) at different frequencies. S21 is a measure ofthe signal coming out port-2 (receiving antenna 303) relative to the RFstimulus entering port-1 (transmitting antenna 301). A vector networkanalyzer is used for obtaining the s21 spectrum and the signal processorof the network analyzer is used for this purpose. The characteristics ofthe sensor affect the electromagnetic wave traveling through itself. Atthe resonance, the sensor structure absorbs the electromagnetic wavethat causes a dip in the s21 spectrum.

In a preferred embodiment the readout mechanism includes two identicalmonopole patch antennas.

In a preferred embodiment the readout circuit for the biosensors isstandalone. The circuit eliminates the need for a vector networkanalyzer. The readout circuit is based on an oscillator circuit thatuses the sensor as a resonator. The ports of the antennas are directlyconnected to the oscillator circuit that oscillates at the resonantfrequency of the sensor. The output of the oscillator circuit is a sinewave at the frequency of the sensor. The frequency of the oscillation isaltered due to the operation of the sensor and can be measured at theoutput of the oscillator circuit.

In a preferred embodiment, the antennas can be located on eyeglasseswhere all the mentioned units can be integrated.

The readout configurations can be various. For example, one readoutconfiguration uses eyeglasses that include the antennas and theinterfacing electronics. The measured pressure can be transmittedwirelessly from the eyeglasses to a display unit or a computer or amobile phone.

Alternatively, another readout configuration is based on the utilizationof hardware and software of a mobile phone for readout purposes. In thisconfiguration, the user wears contact lenses and brings a mobile phonenext to the contact lenses. The integrated Bluetooth antenna of themobile phone can be used to interrogate the sensor wirelessly.

FIG. 2B shows how the s21 spectrum of the device changes with decreasingradius of curvature. The measurement sensitivity is based on the qualityfactor of the resonator and as shown in FIG. 2(b), the quality factordoes not change significantly as a function of radius of curvature. Thegap of the SRR structure decreases as the radius of the curvaturedecreases. This results in an increase in the capacitance of theresonator, so the resonant frequency decreases as shown in FIG. 2C. Werepeated this experiment six times with different substrates and paintedthe SRR structure each time separately after we pumped air such that theradius of the curvature became 13 mm.

FIG. 2C shows the mean values and the standard error mean values of themeasured resonant frequencies normalized to the value we measured forthe radius of curvature of 13 mm. The range of the change in radius ofthe curvature is physiologically relevant to the diagnosis of glaucoma.The result of an experiment conducted with 16 fresh porcine eyes, byapplying five consecutive incremental 100 μl injections, suggests thatwith each incremental injection of fluid, intraocular pressure andradius of curvature of the sclera increases linearly from 9 mm to 13 mm.

An increase in radius of curvature (as a result of a change inintraocular pressure) means the painted (or the printed) ring on thesurface of a contact lens will have a larger surface area whilepreserving its volume. So, its width and gap will increase while itsheight decreases. In addition, the deformed shape alters the operationof the device and introduces additional effects that are not expressedin above Equations 1-3. So, it is important to experimentallycharacterize the sensor within the radii of curvature of interest. FIG.2(c) indicates the resonant frequency increases with increasing radiusof curvature within the probed range. The sensitivity is based on thequality factor of the resonator and as shown in FIG. 2(b), the qualityfactor does not change significantly as a function of radius ofcurvature.

What is claimed is:
 1. A biomedical pressure sensing system comprising:a contact lens; a flexible resonator embedded in the contact lens; andmeasuring means for transmitting and receiving signals and measuringdifferences between the transmitted signal and received signal.
 2. Thebiomedical pressure sensing system of claim 1, wherein the measuringmeans is an antenna pair, placed at proximity of the flexible resonator,the antenna pair including a transmitting antenna and a receivingantenna; wherein the transmitting antenna sends electromagnetic wave tothe flexible resonator; the receiving antenna captures theelectromagnetic wave from the flexible resonator, the capturedelectromagnetic wave is converted into a signal; wherein the systemfurther includes a readout circuit, configured to process the signalfrom the receiving antenna.
 3. The biomedical pressure sensing systemaccording to claim 2, wherein the flexible resonator is a split-ringwhich includes a gap and two extension portions at both ends of the gap;and the flexible substrate is made of cellulose acetate.
 4. Thebiomedical pressure sensing system according to claim 3, wherein aninductance of the split-ring is expressed the following equation:$L = {\mu_{0}{R_{m}\left( {{\log \frac{8R_{m}}{h + w}} - \frac{1}{2}} \right)}}$wherein μ₀ is free-space permeability, R_(m) is effective radius of thesplit-ring, w is a width of the split-ring, and h is a height of thesplit-ring.
 5. The biomedical pressure sensing system according to claim3, wherein a capacitance of the gap is calculated as follows:$C_{gap} = {{ɛ_{0}\frac{hw}{g}} + C_{0}}$ wherein ε₀ is free-spacepermittivity, C0 is the capacitance caused by fringing fields and can becalculated as C₀=ε₀(h+w+g).
 6. The biomedical pressure sensing systemaccording to claim 3, wherein the split-ring has a resonant frequency inS-band which is 2-4 GHz of an electromagnetic band.
 7. The biomedicalpressure sensing system according to claim 3, wherein the split-ring ismade of a silver conductive paint.
 8. The biomedical pressure sensingsystem according to claim 3, wherein a thickness of the split-ring is500 μm.
 9. The biomedical pressure sensing system according to claim 3,wherein a width of the split-ring is 1.5 mm and a length of theextension portion is 3.5 mm.
 10. The biomedical pressure sensing systemaccording to claim 3, wherein a width of the gap is 1 mm.